In this project, the basic mechanisms underlying the elevation in triglyceride and reduction in HDL cholesterol which is found in patients with non-insulin dependent diabetes (NIDDM) will be explored. Patients with untreated NIDDM will be studied following a standard lipid meal challenge before and after institution of tight diabetic control. Alterations in the plasma levels of postprandial lipoproteins including chylomicron remnants, VLDL and HDL will be characterized as well as alterations in the mass and activity of cholesterol ester transfer protein and mass and activity of hepatic lipase. Specific antibodies for apoproteins B100 and B48 will be used to separate hepatogenous and intestinal triglyceride rich lipoproteins for compositional analysis and interaction with cells including fibroblasts, macrophages and endothelial cells. The applicants wish to ascertain the contribution of hepatogenous triglyceride rich particles to the postprandial hypertriglyceridemia of hypertriglyceridemic diabetic subjects. HDL particles of varying lipid composition will also be isolated and infused into rabbits to allow the metabolic clearance rate of their contained apo A-I to be studied. These analyses will be made to test the hypothesis that hypertriglyceridemia induces changes in HDL that facilitate their removal from the circulation. To further define the basis of these metabolic abnormalities, a collaborative study will be undertaken with Dr. Jean MacCluer and investigators at University of Texas, San Antonio, to determine if there is a familial aggregation of the elevated triglyceride and/or low HDL cholesterol in the Mexican American population and if familial aggregation is related to that of diabetes.